Safety and Feasibility of Irradiation and Nivolumab in Esophageal Cancer Cohorts – (INEC study) – A Phase I/II trial (CA209-9M9 study)
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- Safety: The primary end point in this study is safety measurements done to determine the safety profile of the treatment; safety parameters included adverse events, biochemistry, hematology, vital signs and performance status. Adverse events are recorded according to CTCAE v5.0 (CTCAE grade 2-5 rate).
研究概览
简要总结
Safety measurements done to determine the safety profile of the treatment; safety parameters included adverse events, biochemistry, hematology, vital signs and performance status. Adverse events are recorded according to CTCAE v5.0 (CTCAE grade 2-5 rate)
详细描述
Three parallel cohort, multicenter, open-label, phase I/II clinical trial to analyze the safety and feasibility of PD-1 inhibition with Nivolumab given concomitantly with standard radiotherapy regimens in the treatment of esophageal cancer.
Cohort A: Advanced/inoperable esophageal cancer, eligible for palliative radiotherapy of the primary tumor.
Cohort B: Inoperable esophageal cancer without metastases, eligible for definitive chemoradiotherapy Cohort C: Operable esophageal cancer eligible for neoadjuvant chemoradiotherapy
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 years 至 65+ years（65+ Years, 18-64 Years）
- 接受健康志愿者
- 否
入选标准
- •Age > 18 years
- •Specific inclusion criteria - Cohort A:
- •Eligible for palliative fractionated radiotherapy of the esophageal- or gastroesophageal cancer as determined by the multidisciplinary team (MDT) meeting.
- •Expected survival >3 months.
- •Not bulky disease, i.e. palliative radiotherapy towards the primary tumor is intended to palliate dysphagia and/or pain and systemic treatment could be delayed to AFTER protocol therapy if possible.
- •Specific inclusion criteria – Cohort B:
- •Eligible for definitive chemoradiation of localized but inoperable esophageal- or gastroesophageal cancer as determined by the multidisciplinary team (MDT) meeting.
- •Regional disease, i.e. no metastasis outside the radiation field (PTV).
- •Considered candidate/ able to adhere to the intended chemoradiotherapy
- •Specific inclusion criteria – Cohort C:
- •Eligible for neoadjuvant chemoradiotherapy and surgery of the esophageal- or gastroesophageal cancer as determined by the multidisciplinary team (MDT) meeting.
- •Regional disease, i.e. no metastasis outside the radiation field (PTV).
- •Considered candidate and able to adhere to the intended neoadjuvant chemoradiotherapy and planned surgery.
- •Patients should have previously untreated histologically proven squamous cell carcinoma or adenocarcinoma of the esophagus or the gastroesophageal junction (GEJ), Siewert I, II or III
- •Must be ambulatory with a performance status ECOG 0 or 1
- •Adequate organ function based on clinical examiniation and lab values as defined in the below: Absolute neutrophil count: ≥ 1,5 x109/L Platelets: ≥ 100 x109/L Hemoglobin: ≥ 9 x109/L Creatinine ≤ 1,5 upper limit normal (ULN) OR measured/calculaterd GFR≥60 mL/min Albumin ≥ 30 g/L Total bilirubin ≤ 1,5 ULN ASAT and ALAT ≤ 2,5 ULN, or ≤ 5 ULN for subjects with liver mets. International Normalized Ratio (INR) ≤ 1,5 ULN and Activated Partial Thromboplastin Time (TT) ≤ 1,5 ULN unless subject is receiving anticoagulant therapy. Such therapy (if indicated) should be converted to adequate therapy with low-molecular weight heparin such as Dalteparin before chemotherapy or treatment with IMP.
- •Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 28 days prior to the start of study drug (screening phase). Women must not be breastfeeding.
- •WOCBP should use highly effective adequate method to avoid pregnancy for 23 weeks (30 days plus the time required for Nivolumab to undergo five half-lives) after the last dose of investigational drug. Adequate methods are described in Appendix I.
- •Males who are sexually active with WOCBP must agree to follow instructions for method(s) of contraception during the study treatment period and until 7 months after last dose of Nivolumab
- •Signed informed consent and expected cooperation of the patients for the treatment and follow up must be obtained and documented according to ICH GCP, and national/local regulations.
- •If Dysphagia score >2, a nasogastric feeding tube should be inserted during the aid of gastroscopy, and nasogastric tube feeding started before radiotherapy.
排除标准
- •Previous treatment with radiotherapy towards volumes within the thoracic cavity
- •History of prior malignancy within the last 5 years, excluding curatively treated basal cell or squamous cell carcinoma of the skin.
- •Known history of brain metastases
- •Need to use immunosuppressive drugs including, but not limited to: Glukocorticoids, everolimus, sirolimus, disease-modifying anti-rheumatic drugs (DMARDS)
- •Positive pregnancy test (positive hCG blood test)
- •Known allergy, hypersensitivity, or contraindication to the investigational product Nivolumab, or the drugs paclitaxel and docetaxel used in the standard chemoradiotherapy protocols (Cohorts B and C) or any components used in their preparation or has a contraindication to taxane therapy.
- •Any reason why, in the opinion of the investigator, the patient should not participate.
- •Previous treatment with any PD-1 or PD-L1/2 inhibitor
- •Hypersensitivity to the investigational product or any of the drug formula contents
- •Esophageal stenting
- •T4b if infiltration into the aorta or the trachea
- •History of prior autoimmune disorders requiring systemic therapy (excluding Insulin or Thyroid replacement therapy)
- •History of HIV 1 /2, Hepatitis B or C infection
- •History of Immunodeficiency disorders (i.e. immunoglobulin deficiency or white blood cell lineage depletion disorders)
- •Participation in any other interventional clinical trial with an investigational product
结局指标
主要结局
Safety: The primary end point in this study is safety measurements done to determine the safety profile of the treatment; safety parameters included adverse events, biochemistry, hematology, vital signs and performance status. Adverse events are recorded according to CTCAE v5.0 (CTCAE grade 2-5 rate).
Safety: The primary end point in this study is safety measurements done to determine the safety profile of the treatment; safety parameters included adverse events, biochemistry, hematology, vital signs and performance status. Adverse events are recorded according to CTCAE v5.0 (CTCAE grade 2-5 rate).
Feasibility: The feasibility of conducting the study will be reported as number of patients screened, and number of patients successfully included into the study per one year of accrual time.
Feasibility: The feasibility of conducting the study will be reported as number of patients screened, and number of patients successfully included into the study per one year of accrual time.
次要结局
- Overall Survival: The time from onset of treatment (day 1) to death from any cause.
- Infield and Outfield Response to Treatment: The response rate as measured by RECIST 1.1 and immune-related RECIST (ir-RECIST) within the irradiated volume (infield) verses outside the irradiated volume (outfield).
- Progression Free Survival (Only Cohort B): The time from treatment start (day -21) until the disease progresses (PD) as determined by investigators from tumor assessments per RECIST or death from any cause.
- Disease Free Survival (Only Cohort C): The time from surgery until recurrency or occurrence of disease progression as determined by investigators from tumor assessments per RECIST.
- Pathology Complete Response Rate (Only Cohort C): The complete response rate in the surgical specimen by Chirieac grading by pathologist.
- Quality of Life:Quality of Life Questionnaires (QLQ) by patient reported outcomes EORTC QLQ-C30, EORTC QLQ-OG25 and EQ-5D.
研究者
Department of Clinical Cancer Research
Scientific
Oslo University Hospital HF